The proliferative and differentiation capacities of immunocompetent cells decrease with increasing age. Consequently, certain normal immunologic functions decline. Functional alteration of precursor cells may reflect a genetically programmed postmaturation event or a stochastic event. The objectives of this project are (a) to determine the mechanisms responsible for functional alterations of immunocompetent precursor cells and (b) to develop methods for controlling age-related decline in normal immunologic functions. The results of studies in progress indicate that (a) the proliferative capacity of old stem cells is reduced due to age-related changes in the cells and in their environment, (b) certain T cell differentiation capacities decreased abruptly and early in life, whereas others seem to continue throughout life but with a declining efficiency, (c) bovine thymosin had no appreciable enhancing effect on the proliferative capacity of T and B cells of old long-lived mice, and (d) both the proliferative and humoral helper activities of old T cells can be enhanced significantly with mercaptoethanol treatment.